Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
  • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
  • C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
  • C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D307/32—Oxygen atoms
  • C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C255/00—Carboxylic acid nitriles
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
  • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
  • C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/597—Unsaturated compounds containing a keto groups being part of a ring of a five-membered ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/687—Unsaturated compounds containing a keto groups being part of a ring containing halogen
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
  • C07D303/02—Compounds containing oxirane rings
  • C07D303/38—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D303/40—Compounds containing oxirane rings with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals by ester radicals
  • C07D303/42—Acyclic compounds having a chain of seven or more carbon atoms, e.g. epoxidised fats
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D315/00—Heterocyclic compounds containing rings having one oxygen atom as the only ring hetero atom according to more than one of groups C07D303/00 - C07D313/00

Definitions

• the present invention relates to a process for preparing 2-alkylcyclopent-2-enones having the formula: ##STR3## wherein R represents one of the following groups: C n H 2n+1 (the chain being linear or branched);
• n ranges from 1 to 20 and R' is an alkyl radical containing up to 5 carbon atoms, a benzyl radical or a phenyl radical, these last two radicals optionally carrying, in the aromatic nucleus, one or more substituent groups (inert under the reaction conditions).
• Cyclopentenones (I) are useful intermediates for the manufacture of pharmaceutical products and of drugs for veterinary use, in particular, prostaglandins.
• an olefin is reacted, in a first step, with trihydrated manganese acetate, potassium permanganate, acetic anhydride and anhydrous sodium acetate, all in a large excess with respect to the olefin, thereby obtaining a ⁇ -alkyl lactone, which, in a second step, is cyclized by means of polyphosphoric acid, thereby obtaining the final product.
• Such a process gives rise to low yields and requires particular reactants which are expensive and can be handled only with difficulty; furthermore, the reactions lead to complex mixtures of products from which the ⁇ -alkyl lactone and the final product may be separated only with difficulty.
• An object of the invention is to provide a process for the preparation of 2-alkylcyclopent-2-enones having formula (I) with rather good yields, and a second object is to provide a process starting from raw materials which are cheap and can be handled easily.
• a third object is to provide a process allowing the intermediate products and the final product to be separated easily.
• epoxide (III) is reacted, under reflux conditions, with an alkylating agent having the formula: ##STR5## (where R" is an ethyl, an isopropyl, or an isobutyl radical) in the presence of a malonic ester having the formula:
• said lactone (V) is reacted at 20° to 100° C. with a protic acid, thereby obtaining, by cyclization, the desired 2-alkylcyclopent-2-enone having the formula (I).
• n ranges preferably from 1 to 10.
• the preferred substituent groups are C n H 2n+1 or (CH 2 ) n -COOR'.
• radical R' is a benzyl or a phenyl radical
• these groups may be substituted in the aromatic nucleus by one or more inert groups (usually from 0 to 2), selected generally from the class consisting of NR 2 '", OR'", X, CN and NO 2 , where X has the meaning given above and where R'" is an alkyl radical containing up to 5 carbon atoms, a benzyl radical or a phenyl radical.
• the oxidation of the olefin CH 2 ⁇ CH--CH 2 --R to the epoxide ##STR8## may be carried out by means of well-known methods, according to which the substituents, optionally present in group R, remain unaltered.
• a suitable method resides in oxidizing the olefin by means of m-chloroperbenzoic acid; such method providing the epoxide with yields over 90% and allowing of a very simple working.
• Another suitable method resides in oxidizing the olefin with H 2 O 2 in the presence of a catalyst based on tungstate and phosphate ions; such a method is described, for instance, in an article by C. Venturello et al, on the J. Org. Chem., 48, 13831, 1983. This last method is more economical than the first one, giving rise to good epoxide yields (about 70%), and allowing one to recover much of the non-reacted olefin. It is clear that still other methods may be used, provided that they do not alter the substituents optionally present in group R.
• the second step resides in alkylating epoxide (III) by means of an alkylating agent Na + [CH(COOR") 2 ] - , wherein R" is an ethyl, an isopropyl, or an isobutyl radical; the reaction is described, for instance, in an article by C. H. Depuy et al, in the J. Org. Chem., 1964, page 2810, the reaction scheme being: ##STR9##
• the epoxide is reacted with the above-mentioned alkylating agent in the presence of a malonic ester having the formula
• the alkylating agent should be used in a substantially equimolar ratio with respect to the epoxide, and said malonic ester should be used in a molar ratio with respect to the epoxide of from 0.5 to 2; preferably, such molar ratio should be about 1.
• the reaction must be carried out under reflux conditions.
• the alkylation of epoxide (III) turned out to be completely regioselective, providing only the attack product in the non-substituted position.
• ⁇ -carboxy- ⁇ -alkyl lactone (IV) is then saponified in an alkaline medium, thereby obtaining the corresponding acid (VI): ##STR10##
• This reaction may be carried out as follows: an aqueous solution of sodium carbonate is added to the reaction mixture of the preceding step and the two phases are mixed generally at from 50° C. to the reflux temperature.
• Acid (VI) may be separated from the reaction mixture as follows: alcohol R"OH is distilled, while leaving the acid in the aqueous phase and separating said acid successively by crystallization or by extraction by means of an organic solvent.
• Acid (VI) is then decarboxylated, at 100° to 160° C., thereby obtaining a ⁇ -alkyl lactone having the formula: ##STR11##
• the decarboxylation should be carried out preferably at 120° to 140° C.
• Some of the ⁇ -alkyl lactones may be used for perfumes or essential oils.
• ⁇ -alkyl lactone (V) is then reacted at 20° to 100° C. (preferably 50° to 60° C.), with a protic acid, thereby obtaining, by cyclization, the desired 2-alkyl-cyclopent-2-enone having the formula (I).
• the protic acids are generally selected from the group consisting of polyphosphoric acid, 96% sulphuric acid (weight/volume), and a mixture consisting of CH 3 --SO 3 H and P 2 O 5 .
• the mixture consisting of CH 3 --SO 3 H and P 2 O 5 turned out to be particularly suitable.
• the CH 3 --SO 3 H/P 2 O 5 weight ratio usually ranged from 10 to 20, and is preferably equal to about 10.
• the preparation of the mixture consisting of CH 3 --SO 3 H and P 2 O 5 is described, for instance, in an article by P. E. Eaton et al, J. Org. Chem., 38, 4071, 1973, and the cyclization reaction by means of a protic acid is described, for instance in an article by E. Uhlig et al, Adv. Org. Chem., 1, 35, 1960.
• the reaction may be carried out as follows: ⁇ -alkyl lactone (V) is added to the protic acid, at room temperature.
• the resultant solution is heated, as described above, for a time generally ranging between 5 and 24 hours, depending on the nature of substituent R.
• the solution is poured into water and the resultant solution is extracted by means of an organic solvent immiscible with water.
• the organic phase is separated, dehydrated and concentrated in order to yield an oil.
• the product is then isolated by distillation under reduced pressure, by crystallization or by separation on a chromatographic column, or by the combined use of two of these techniques.
• the first four steps give rise to a high yield; therefore, the global or overall yield of the process is good;
• the intermediate products and the final product may be easily separated.
• the thus-obtained oil was distilled under reduced pressure (108° to 110° C./2.10 -1 mm Hg), thereby providing 52.5 g (0.23 moles) of ethyl 10,11-epoxydecanoate, with a yield of 92%.
• This oil was treated with diazomethane (CH 2 N 2 ) in order to form the methyl ester of the desired product.
• the resultant oil was conveyed onto a silica gel column, using hexane-ether as eluent in a 1:1 ratio by volume. Two fractions were recovered:
• the yield of the latter was 41%.
• the molar ratio between the cyclohexenone and the cyclopentenone was 4:1.

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• 1985
  • 1985-03-05 IT IT19770/85A patent/IT1200400B/it active
• 1986
  • 1986-03-03 JP JP61044318A patent/JPS61218549A/ja active Pending
  • 1986-03-03 CA CA000503154A patent/CA1271488A/en not_active Expired
  • 1986-03-03 US US06/835,246 patent/US4673759A/en not_active Expired - Fee Related
  • 1986-03-05 EP EP86301568A patent/EP0194144B1/en not_active Expired - Lifetime
  • 1986-03-05 DE DE8686301568T patent/DE3681307D1/de not_active Expired - Lifetime

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